47: Hereditary Pheochromocytoma and Paraganglioma

Key Points

• Disease summary:

  • Paraganglia are clusters of neuroendocrine cells that comprise the sympathetic ganglia, the parasympathetic ganglia, and the adrenal medulla. A paraganglioma (PGL) is a tumor that derives from paraganglia.

  • The term pheochromocytoma (PHEO) is applied to catecholamine-secreting paragangliomas of the adrenal gland.

  • Extra-adrenal paragangliomas (ePGLs) may be categorized as either sympathetic (usually found in the abdomen) or parasympathetic (usually found in the head and neck; hnPGL) paragangliomas.

  • PHEOs and ePGLs most commonly present with hypertension, headache, anxiety, and/or palpitations.

  • hnPGLs usually present as an enlarging mass or with a mass effect such as a cranial nerve palsy (eg, Horner syndrome).

  • PGLs have an estimated prevalence of 1 in 5000 and an estimated incidence of 1 in 30,000.

• Hereditary basis:

  • Approximately 30% of PGLs are associated with an identifiable germline mutation; two-thirds of these cases are apparently sporadic.

    • The likelihood that a germline mutation is present is strongly influenced by the clinical presentation: presence of syndromic features, presence of a family history, tumor location, age of diagnosis, greater than one primary PGL or metastatic disease.

    • At least 10 PHEO- or PGL-predisposing genes have been identified.

• PGLs show an autosomal dominant inheritance pattern with incomplete penetrance.

  • The tumor risk associated with several genes is influenced by the parent of origin (SDHD, SDHAF2, MAX) where tumor risk is associated with paternal inheritance.

• Differential diagnosis:

  • It is important to distinguish the multiorgan system syndromes that include PHEO or PGLs as a single feature (ie, von Hippel-Lindau [VHL], neurofibromatosis [NF], and multiple endocrine neoplasia [MEN]), from the familial tumor predispositions in which these tumors are the predominant feature (Table 47-1).